The present invention relates to a process for preparing chiral 1,2-diols from olefins using catalysts based on osmium compounds. Chiral 1,2-diols are of industrial importance as fine chemicals and as intermediates for pharmaceuticals and for active compounds in the agrochemicals sector.
The standard method of synthesizing chiral 1,2-diols is the Sharpless dihydroxylation reaction in which olefins are reacted in the presence of osmium tetroxide, chiral nitrogen ligands and superstoichiometric amounts of potassium hexacyanoferrate and potassium carbonate as oxidant. Review articles describing this methodology may be found, for example, in xe2x80x9cAsymmetric Dihydroxylation Reactionsxe2x80x9d M. Beller, K. B. Sharpless, in B. Cornils, W. A. Herrmann (Eds.) VCH, 1996, Weinheim, and H. C. Kolb, M. S. Van Nieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483.
A critical disadvantage of the Sharpless dihydroxylation is the use of a number of equivalents of potassium hexacyanoferrate as oxidant (Y. Ogino, H. Chen, H. L. Kwong, K. B. Sharpless, Tetrahedron Lett. 1991, 32, 3965). Apart from the cost of the oxidant, the formation of large amounts of salt and metal wastes is, in particular, ecologically disadvantageous. Thus, both the price and the superstoichiometric amount of the iron complex to be used (3 mol=990 g per 1 mol of substrate) with addition of potassium carbonate (3 mol=420 g) is a considerable disadvantage in a synthesis of the diols on a relatively industrial scale. Processes for the electrochemical oxidation of the Na4[Fe(CN)6] formed in the reaction to Na3[Fe(CN)6] (Sepracor Inc. (Y. Gao, C. M. Zepp), PCT Int. Appl. WO 9.317.150, 1994; Anon., Chem. Eng. News, 1994, 72 (24), 41) are also difficult to implement on an industrial scale since electrochemical processes are generally too expensive due to the apparatus required.
Although the literature discloses less expensive oxidants for dihydroxylations (for example chlorates; K. A. Hofmann, Chem. 1912, 45, 3329; H2O2 in tert-butanol: N. A. Milas, J.-H. Trepagnier, J. T. Nolan, M. Ji. Iliopolus, J. Am. Chem. Soc. 1959, 81, 4730: tert-butyl hydroperoxide in the presence of Et4NOH; K. B. Sharpless, K. Akashi, J. Am. Chem. Soc. 1976, 98, 1986: P. H. J. Carisen, T. Katsuki, V. S. Martin, K. B. Sharpless, J. Org. Chem. 1981, 46, 3936; F. X. Webster, J. Rivas-Enterrios, R. M. Silverstein, J Org. Chem. 1987, 52, 689; V. S. Martin, M. T. Nunez, C. E. Tonn, Tetrahedron Lett. 1988, 29, 2701; M. Caron, P. R. Carlier, K. B. Sharpless, J Org. Chem. 1988, 53, 5185, tertiary amine oxides and, in most cases, N-methylmorpholine N-oxide; W. P. Schneider, A. V. Mcintosh, U.S. Pat. No. 2.769.824 (1956); V. Van Rheenen, R. C. Kelly, D. Y. Cha, Tetrahedron Lett. 1976, 17, 1973), none of the processes mentioned allow preparation of chiral diols with good enantioselectivities.
To avoid the indicated disadvantages of the known catalytic process using potassium hexacyanoferrate, it is an object of the invention to develop a novel process for asymmetric dihydroxylation which gives chiral 1,2-diols in high yield, enantioselectivity and purity using an inexpensive reoxidant and which is suitable for industrial implementation.
This object is achieved by a process for the asymmetric dihydroxylation of olefins by means of osmium catalysts, in which, according to the invention, monofunctional, bifunctional and/or polyfunctional 1,2-diols of the formula (I)
R1R2C(OH)xe2x80x94C(OH)R3R4xe2x80x83xe2x80x83(I)
where
R1 to R4 are each, independently of one another, hydrogen, alkyl, CN, COOH, COO-alkyl, COO-aryl, CO-alkyl, CO-aryl, O-alkyl, O-aryl, O-CO-aryl, O-CO-alkyl, OCOO-alkyl, N-alkyl2, NH-alkyl, N-aryl2, NH-aryl, NO, NO2, NOH, aryl, fluorine, chlorine, bromine, iodine, NO2, Si-alkyl3, CHO, SO3H, SO3-alkyl, SO2-alkyl, SO-alkyl, CF3, NHCO-alkyl, CONH2, CONH-alkyl, NHCOH, NHCOO-alkyl, CHCHCO2-alkyl, CHCHCO2H, PO-(aryl)2, PO-(alkyl)2, PO3H2, PO(O-alkyl)2, where alkyl represents an aliphatic organic group having from 1 to 18 carbon atoms which may be linear, branched and/or cyclic and aryl is a five-, six- or seven-membered aromatic ring which contains from 4 to 14 carbon atoms and may be fused and contain from 0 to 3 hetero atoms such as N, O, S and where the alkyl and/or the aryl group may bear up to six further substituents selected independently from among hydrogen, alkyl, O-alkyl, OCO-alkyl, O-aryl, aryl, fluorine, chlorine, bromine, iodine, OH, NO2, NO, Si-alkyl3, CN, COOH, CHO, SO3H, NH2, NH-alkyl, N-alkyl2, PO-alkyl2, SO2-alkyl, SO-alkyl, CF3, NHCO-alkyl, COO-alkyl, CONH2, CO-alkyl, NHCOH, NHCOO-alkyl, CO-aryl, COO-aryl, PO-aryl2, PO3H2, PO(O-alkyl)2, SO3-alkyl, where alkyl and aryl are as defined above,
are obtained by reacting olefins of the formula (II)
R1R2Cxe2x95x90CR3R4xe2x80x83xe2x80x83(II)
where
R1 to R4 are as defined above,
with molecular oxygen in the presence of a catalytic amount of an osmium compound and a chiral amine in water or a water-containing solvent mixture at a pH of from 7.5 to 13.
In particular, compounds of the formula (I) are prepared using olefins of the formula (II) in which the substituents R1 to R4 are each, independently of one another, hydrogen, alkyl, CN, COOH, COO-alkyl, COO-aryl, CO-alkyl, CO-aryl, O-alkyl, O-aryl, N-alkyl2, aryl, fluorine, chlorine, bromine, iodine, CHO, CF3, NHCO-alkyl, CONH2, CONH-alkyl, NHCOO-alkyl. Here, alkyl and aryl are as defined above.
Particular preference is given to a process in which diols of the formula (I) in which R1 to R4 are each, independently of one another, hydrogen, alkyl, CN, COOH, COO-alkyl, CO-alkyl, CO-aryl, O-alkyl, O-aryl, aryl, fluorine, chlorine, bromine, CHO, NHCO-alkyl. Here alkyl and aryl are as defined above.
The process of the invention is carried out in the presence of water. It has been found to be advantageous to use a further organic solvent in addition to the olefin. The process of the invention can also, in the case of various olefins, be carried out in the olefin/water mixture without further solvent. Further solvents used are generally inert organic solvents. Suitable solvents are aliphatic ethers, aromatic or aliphatic hydrocarbons, alcohols and esters, halogenated hydrocarbons, dipolar aprotic solvents such as dialkyl sulfoxides, N,N-dialkylamides of aliphatic carboxylic acids and also mixtures thereof. Preference is given to alcohols, esters and ethers. The aqueous phase used is generally a basic aqueous solution having a pH of from 7.5 to 13. The basic pH of the solution is achieved by addition of a base to the water. In general, it is advantageous to carry out the process in buffered aqueous solutions, preferably at a pH of from 8 to 13. The buffered solution is prepared by addition of known buffers to water.
To enable the diol products to be separated off readily, it is sometimes advantageous to use an aqueous salt solution or buffered aqueous salt solution, for example an aqueous solution of an alkali metal halide or alkaline earth metal halide, as solvent in place of water or buffered aqueous solutions.
The oxidant used in the process of the invention is molecular oxygen or a gas mixture comprising molecular oxygen. Preference is given to gas mixtures comprising at least 15% by volume of oxygen. Particular preference is given to air and oxygen gas having an oxygen content of  greater than 95%.
The reaction preferably proceeds at temperatures of from 20 to 150xc2x0 C. In many cases, it has been found to be useful to employ temperatures of from 30 to 120xc2x0 C., preferably from 40 to 80xc2x0 C. The process of the invention can be carried out at atmospheric pressure, e.g. by passing oxygen through the reaction solution. However, a faster reaction rate can be achieved when a superatmospheric pressure of oxygen is employed. The process can be carried out at pressures of up to 200 bar, but is usually carried out at a pressure of not more than 60 bar and preferably in the range from atmospheric pressure to 20 bar.
Chiral ligands used are chiral amines known from the literature (H. C. Kolb, M. S. Van Nieuwenhze"", and K. B. Sharpless, Chem Rev. 1994, 94, 2483-2547), for example diaminocyclohexane derivatives, substituted diaminoethanes, bispiperazine, bispyrrolidine, bistetrahydropyridine compounds, 1,4-diazabicyclo[2.2.2]octane derivatives, substituted isooxazolidines, in particular (DHQD)2PHAL (hydroquinidine 1,4-phthalazinediyl diether) and (DHQ)2PHAL (hydroquinine 1,4-phthalazinediyl diether) and (DHQ)2Pyr (hydroquinine 2,5-diphenyl-4,6-pyrimidinyl diether).
The osmium catalysts used are generally osmium compounds in the oxidation states +8 and +6. However, it is also possible to use osmium catalyst precursors in low oxidation states. These are converted under the reaction conditions into the catalytically active Os(VIII) and Os(VI) species. As osmium catalysts or catalyst precursors, it is possible to use, for example, OsO4, K2Os2(OH)4, Na2Os2(OH)4, Os3(CO)12, OsCl3, H2OsCl6, [CF3SO3Os(NH3)5](O3SCF3)2, OsO4 on vinylpyridine, ButNOsO3.
In the process of the invention, the osmium catalyst is used in catalytic amounts relative to the olefin. In general, use is made of from 0.2 to 0.00001 equivalents, based on olefin, preferably from 0.1 to 0.0001 equivalents and particularly preferably from 0.08 to 0.0005 equivalents.
The ratio of amine to osmium is from 0.01:1 to 1 000:1, preferably from 0.1:1 to 100:1. Particular preference is given to using ratios of amine to osmium of from 1:50 to 50:1.
When using bulky olefins, in particular trisubstituted and tetrasubstituted olefins, it is sometimes advantageous to use a cocatalyst to hydrolyze the osmate ester formed as an intermediate. This cocatalyst is an amide which promotes the hydrolysis, for example a sulfonamide and/or carboxamide. Particular preference is given to the addition of methylsulfonamide.
The cocatalyst is used in an amount of from 0.01 mol % to 10 mol % (based on olefin), preferably from 0.1 to 5 mol %.
The particular advantage of the process of the invention is the use of oxygen or oxygen-containing gases as reoxidant. Despite the comparatively difficult reoxidation process, high enantioselectivities can be achieved. The catalyst productivity can be increased by treating the aqueous catalyst phase which has been used once with olefin again. In this way, the catalyst costs for the process of the invention are minimized, so that even industrial processes can be carried out economically.
The process of the invention is particularly surprising and novel since no asymmetric osmium-catalyzed dihydroxylation reactions to form 1,2-diols using oxygen as reoxidant were known in the past. The novel combination described in the process of the invention of addition of a ligand which accelerates the dihydroxylation and carrying out the process in a strongly basic buffered solution surprisingly leads to an enantioselective dihydroxylation process even in the presence of oxygen. The process of the invention demonstrates for the first time that the statements made in the known literature in respect of osmium-catalyzed dihydroxylation using oxygen are wrong.
The particular advantages of the novel process are the price advantage of the oxidant, the simplicity of the procedure and the high selectivity of the process compared to known processes using potassium hexacyanoferrate.
The chiral 1,2-diols prepared according to the invention can be used, inter alia, as precursors for agrochemicals, cosmetics, pharmaceuticals and chiral polymers.